A new time-dependent density-functional method for molecular plasmonics: Formalism, implementation, and the Au144(SH)60 case study

We describe the implementation and application of a recently developed time-dependent density-functional theory (TDDFT) algorithm based on the complex dynamical polarizability to calculate the photoabsorption spectrum of large metal clusters, with specific attention to the field of molecular plasmonics. The linear response TDDFT equations are solved in the space of the density fitting functions, so the problem is recast as an inhomogeneous system of linear equations whose resolution needs a numerical effort comparable to that of a SCF procedure. The construction of the matrix representation of the dielectric susceptibility is very efficient and is based on the discretization of the excitation energy, so such matrix is easily obtained at each photon energy value as a linear combination of constant matrix and energy-dependent coefficients. The code is interfaced to the Amsterdam Density Functional (ADF) program and is fully parallelized with standard message passing interface. Finally, an illustrative application of the method to the photoabsorption of the Au144(SH)60 cluster is presented

Crystal Structure and Theoretical Analysis of Green Gold Au30(S-tBu)18 Nanomolecules and Their Relation to Au30S(S-tBu)18

We report the complete X-ray crystallographic structure as determined through single-crystal X-ray diffraction and a thorough theoretical analysis of the green gold Au30(S-tBu)18. While the structure of Au30S(S-tBu)18 with 19 sulfur atoms has been reported, the crystal structure of Au30(S-tBu)18 without the \u3bc3-sulfur has remained elusive until now, though matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) data unequivocally show its presence in abundance. The Au30(S-tBu)18 nanomolecule not only is distinct in its crystal structure but also has unique temperature-dependent optical properties. Structure determination allows a rigorous comparison and an excellent agreement with theoretical predictions of structure, stability, and optical response

Computational models of photosensitizers to be used in photodynamic therapy: from assisted delivery to light activation

Tesis Doctoral inédita cotutelada por la Universität de Wien y la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química. Fecha de Lectura 25-02-2019Esta tesis tiene embargado el acceso al texto completo hasta el 25-08-2020Photodynamic therapy is an established treatment against certain types of cancer. This therapy exploits the excited-state reaction of a photosensitizer (PS) with molecular oxygen and/or biomolecules of the cells, after being irradiated with light, resulting in singlet oxygen or other cytotoxic species. The success of this therapy is determined by the double selectivity achievable thanks to the chemical and photophysical properties of the PS, which regulate the selective accumulation in the tumour cells and the production of cytotoxic species, respectively. In this thesis, theoretical modelling has been used to help the design of novel PSs and provide useful insights into chemical problems related to the development of more efficient photodrugs. In the first part of this thesis, BODIPYs were selected as a promising class of novel PS for photodynamic therapy. BODIPYs show many of the desired chemical properties of PSs but, often, their photophysics is not suited for efficient therapeutic effects. The absorption maximum of the unsubstituted BODIPY is blue-shifted with respect to the energetic region adequate to treat deep tumours. Moreover, its strong fluorescence indicates poor intersystem crossing probabilities and thereby small triplet quantum yields, fundamental to produce cytotoxic species. Here, two computational methods, CASPT2 and ADC(2), have been used to explore the excited states topology of this dye. That study provided a detailed photophysical mechanism of the bare BODIPY and determined the accuracy of ADC(2) against CASPT2, which was used as reference, to investigate this family of dyes. Since the parent compound is unsuited for photodynamic therapy applications, meso-substituted BODIPYs carrying halogen atoms have been also investigated in close cooperation with biolitec research GmbH. It was found that conjugated substituents in the meso position shift the absorption maximum to the red; however, they also open a detrimental non-radiative deactivation channel to the ground state mediated by a S1=S0-conical intersection that prevents efficient intersystem crossing. The introduction of heavy atoms increases the intersystem crossing probabilities but lowers the relative energies of the S1=S0-conical intersection, favouring internal conversion to the ground state. As a compromise, a mono-brominated meso-ethyl-BODIPY was selected as best choice to perform non-adiabatic molecular dynamics simulations with the SHARC method. Those calculations complemented the stationary calculations and delivered the actual pathways to populate the triplet manifold and the associated timescales. In the second part of the thesis, the emphasis was put on existing successful photodrugs. Temoporfin is a second-generation PS but is very hydrophobic and presents several issues when administrated to patients. For this reason, an assisted delivery using a liposome carrier is currently being developed to deliver the PS more selectively to the targeted cells and provide a more advantageous distribution of the PS inside them. Here, molecular dynamics simulations were employed to unveil that the origin of the good loading capacity of the vesicles lies on the formation of hydrogen bonds between Temoporfin and the carrier material. Furthermore, the umbrella sampling technique was used to simulate the slow drug delivery process from the liposome to a cell membrane and obtain a free-energy profile. The induced rigidity in the system at the transient structure, again due to the formation of hydrogen bonds, explains the origin of the energy barrier, which is then of entropic nature. Finally, at the conformation corresponding to the free energy minimum, the excited states of the photodrug embedded in the hydrophobic environment were calculated using QM/MM calculations.La terapia fotodinámica es un tratamiento establecido contra específicos tipos de cancer. Esta terapia explota la reacción en el estado excitado de un compuesto fotosensible (PS) con oxígeno molecular y/o biomoléculas celulares después de ser irradiado con luz, resultando en oxígeno singlete u otras especies citotóxicas. El éxito de esta terapia es determinado por la doble selectividad que se consigue gracias a las propiedades químicas y fotofísicas del PS, que regulan respectivamente la acumulacion selectiva en las células tumorales y la producíon de especies citotóxicas. En esta tesis han sido usados modelos teóricos para diseñar nuevos PSs y proporcionar perspectivas útiles sobre problemas químicos relacionados con el desarrollo de foto-medicamentos mas eficientes. En la primera parte de esta tesis, seleccionamos BODIPYs (usados generalmente como tintes) como una clase prometedora de nuevos PS para ser usados en terapia fotodinámica. Los BODIPYs presentan muchas de las propiedades químicas que deseamos que presenten los PS pero sus propiedades fotofísicas generalmente no son adecuadas para efectos terapeuticos que sean eficientes. El máximo de absorción del espectro visible del BODIPY más sencillo está desplazado al azul con respecto de la region energética adecuada para tratar los tumores mas internos. Ademas su fuerte fluorescencia indica una baja probabilidad de cruce entre sistemas y por lo tanto rendimientos cuánticos de triplete bajos, que son fundamentales para producir especies citotóxicas. En este estudio hemos usado dos métodos computacionales CASPT2 y ADC(2) para explorar la topologia de los estados excitados de este tinte. Ese estudio proporcionó un mecanismo fotofísico detallado del BODIPY más simple y determinó la exactitud de ADC(2) frente a CASPT2, que fue usado como referencia para investigar esta familia de tintes. Como el compuesto base no es adecuado para aplicaciones en terapia fotodinámica, también estudiamos BODIPY meso substituidos que llevan además átomos de halógeno, en cooperación con la empresa biolitec research GmbH. Se descubrió que substituyentes conjugados en posición meso desplazan hacia el rojo el maximo de absorción; sin embargo también abren un indeseado canal de desactivación no radiativo hacia el estado fundamental mediado por una intersección conica S1=S0 que previene un eficiente cruce entre sistemas. La introducción de átomos pesados aumenta la probabilidad de cruce entre sistemas pero disminuye la energía relativa de la interseccíon conica, favoreciendo la conversión interna al estado fundamental. Para llegar a un compromiso, un meso-etil-BODIPY mono-brominado fue seleccionado como el más cualificado para llevar a cabo simulaciones de dinámica molecular no adiabática con el metodo SHARC. Este proceso complementó los calculos estáticos y produjo las rutas más probables para poblar los estados tripletes y los tiempos de reaccíon asociados. En la segunda parte de la tesis, pusimos enfasis en fotomedicamentos existentes que ya han sido utilizados con éxito. Las Temoporfirinas son fotosensibilizadores de segunda generacion muy hidrofobicos que presentan problemas cuando son administrados a pacientes. Por este motivo biolitec research GmbH ha desarrolado una entrega asistida usando un liposoma como portador para poder llevar el fotosensibilizador de un modo más selectivo a las células objetivo y proporcionar una distribución más ventajosa del PS en su interior. En este punto utilizamos simulaciones de dinámica molecular para descubrir que el origen de la gran capacidad de carga de las vesículas proviene de la formación de enlaces de hidrógeno entre el Temoporfin y el material de transporte. Adicionalmente utilizamos el metodo umbrella sampling para simular el lento proceso de transporte desde el liposoma a la membrana celular y obtener así un perfil de energía libre. La rigidez inducida en el sistema en la estructura transitoria, de nuevo debido a la formación de enlaces de hidrógeno, explica el origen de la barrera energetíca, que es de naturaleza entrópica. Finalmente, en la conformación que corresponde al mínimo de energía, los estados excitados del fotomedicamento rodeado por el medio hidrofóbico fueron calculados usando QM/MM

Insight into the optical properties of meso-pentafluorophenyl(PFP)-BODIPY: An attractive platform for functionalization of BODIPY dyes

The pentafluorophenyl (PFP) moiety is an important and versatile substituent in the chemistry of BODIPYs, porphyrins and corroles. The widespread use of PFP meso-substituted compounds, as intermediates in the synthesis of more complex pyrrole derivatives, is the motivation behind this work, which investigates the optical properties of the meso-PFP-BODIPY from a theoretical point of view. From the panoply of computational tools available for this purpose, we have considered the MS-CASPT2//CASSCF multiconfigurational protocol, and other monoreference methods, including time dependent density functional theory, TD-DFT, the second order approximate couple cluster, CC2, and the algebraic diagrammatic construction scheme of the polarization propagator in its second order, ADC(2). We have identified ADC(2) as the most suited method for the characterization of the absorption properties of BODIPYs. Besides its computational efficiency and the small dependence shown towards the basis set flexibility, the results obtained with this method are independent from the preexisting knowledge of the system and its properties to be calculated by the user. In general, all the methods evaluated show a good performance when compared with experimental results, especially if implicit solvent effects are taken into account, delivering errors which amount to 0.05 eV. Finally, we discuss the effect of the electron-withdrawing PFP substituent at the meso-position on the absorption and emission energies of the boron-dipyrromethene core. The comparison of the PFP-substituted and core BODIPY spectroscopic properties reveals that this substituent red-shifts both the absorption and the emission of the parent dye. On the one hand, the incorporation of this substituent was found to reduce the HOMO-LUMO gap, and on the other it induces a strong destabilization of the electronic ground state along the global coordinate leading the system from the Franck-Condon region to the position of the first excited state, S1, minimum, suggesting a lower S1/S0 internal conversion funnel compared to the parent BODIPY compound.This work has been supported by the Project CTQ2015-63997- C2 of the Ministerio de Economía y Competitividad of Spain. I.C. gratefully acknowledges the “Ramón y Cajal” program of the Ministerio de Economía y Competitividad of Spain. M.D.V. thanks the Marie Curie Actions, within the Innovative Training Network-European Join Doctorate in Theoretical Chemistry and Computational Modelling TCCM-ITN-EJD-642294, for financial suppor

Solvent effects on electronically excited states: QM/Continuum versus QM/Explicit models

The inclusion of solvent effects in the calculation of excited states is vital to obtain reliable absorption spectra and density of states of solvated chromophores. Here we analyze the performance of three classical approaches to describe aqueous solvent in the calculation of the absorption spectra and density of states of pyridine, tropone, and tropothione. Specifically, we compare the results obtained from quantum mechanics/polarizable continuum model (QM/PCM) versus quantum mechanics/molecular mechanics (QM/MM) in its electrostatic-embedding (QM/MMee) and polarizable-embedding (QM/MMpol) fashions, against full-QM computations, in which the solvent is described at the same level of theory as the chromophore. We show that QM/PCM provides very accurate results describing the excitation energies of ππ∗ and nπ∗ transitions, the last ones dominated by strong hydrogen-bonding effects, for the three chromophores. The QM/MMee approach also performs very well for both types of electronic transitions, although the description of the ππ∗ ones is slightly worse than that obtained from QM/PCM. The QM/MMpol approach performs as well as QM/PCM for describing the energy of ππ∗ states, but it is not able to provide a satisfactory description of hydrogen-bonding effects on the nπ∗ states of pyridine and tropone. The relative intensity of the absorption bands is better accounted for by the explicit-solvent models than by the continuum-solvent approach.LG and JJN further acknowledge the University of Vienna for financial support, while MDV and MFSJM thank the Marie Curie Actions, within the Innovative Training Network-European Join Doctorate in Theoretical Chemistry and Computational Modelling TCCM-ITN-EJD-642294, for their respective PhD grant

Assessing Configurational Sampling in the Quantum Mechanics/Molecular Mechanics Calculation of Temoporfin Absorption Spectrum and Triplet Density of States

The absorption properties of Temoporfin, a second-generation photosensitizer employed in photodynamic therapy, are calculated with an electrostatic-embedding quantum mechanics/molecular mechanics (QM/MM) scheme in methanol. The suitability of several ensembles of geometries generated by different sampling techniques, namely classical-molecular-dynamics (MD) and QM/MM-MD thermal sampling, Wigner quantum sampling and a hybrid protocol, which combines the thermal and quantum approaches, is assessed. It is found that a QM description of the chromophore during the sampling is needed in order to achieve a good agreement with respect to the experimental spectrum. Such a good agreement is obtained with both QM/MM-MD and Wigner samplings, demonstrating that a proper description of the anharmonic motions of the chromophore is not relevant in the computation of the absorption properties. In addition, it is also found that solvent organization is a rather fast process and a long sampling is not required. Finally, it is also demonstrated that the same exchange-correlation functional should be employed in the sampling and in the computation of the excited states properties to avoid unphysical triplet states with relative energies close or below 0 eV

Photoabsorption of Icosahedral Noble Metal Clusters: An Efficient TDDFT Approach to Large-Scale Systems

7noWe apply a recently developed time-dependent density functional theory (TDDFT) algorithm based on the complex dynamical polarizability to calculate the photoabsorption spectrum of the following series of closed-shell icosahedral clusters of increasing size (namely, [M13]5+, [M55]3−, [M147]−, and [M309]3+ with M = Ag, Au), focusing in particular on their plasmonic response. The new method is shown to be computationally very efficient: it simultaneously retains information on the excited-state wave function and provides a detailed analysis of the optical resonances, e.g., by employing the transition contribution map scheme. For silver clusters, a very intense plasmon resonance is found for [Ag55]3−, with strong coupling among low-energy single-particle configurations. At variance, for gold clusters we do not find a single strong plasmonic peak but rather many features of comparable intensity, with partial plasmonic behavior present only for the lowest-energy transitions. Notably, we also find a much greater sensitivity of the optical response of Ag clusters with respect to Au clusters to cluster charge, the exchange-correlation (xc) functional, and the basis set, as demonstrated via a detailed comparison between [Ag55]q and [Au55]q. The results of the TDDFT algorithm obtained with the complex dynamical polarizability are finally compared with those produced by alternative (real-time evolution or Lanczos) approaches, showing that, upon proper choice of numerical parameters, overall nearly quantitative agreement is achieved among all of the considered approaches, in keeping with their fundamental equivalence.partially_openopenBaseggio, Oscar; De Vetta, Martina; Fronzoni, Giovanna; Stener, Mauro; Sementa, Luca; Fortunelli, Alessandro; Calzolari, ArrigoBaseggio, Oscar; De Vetta, Martina; Fronzoni, Giovanna; Stener, Mauro; Sementa, Luca; Fortunelli, Alessandro; Calzolari, Arrig

Ligand-Enhanced Optical Response of Gold Nanomolecules and Its Fragment Projection Analysis: The Case of Au30(SR)18

8siHere we investigate via first-principles simulations the optical absorption spectra of three different Au30(SR)18 monolayer-protected clusters (MPC): Au30(StBu)18, Au30(SPh)18, and Au30(SPh-pNO2)18. Au30(StBu)18 is known in the literature, and its crystal structure is available. In contrast, Au30(SPh)18 and Au30(SPh-pNO2)18 are two species that have been designed by replacing the tertbutyl organic residues of Au30(StBu)18 with aromatic ones so as to investigate the effects of ligand replacement on the optical response of Au nanomolecules. By analogy to a previously studied Au23(SR)16 − anionic species, despite distinct differences in charge and chemical composition, a substantial ligand enhancement of the absorption intensity in the optical region is also obtained for the Au30(SPh-pNO2)18 MPC. The use of conjugated aromatic ligands with properly chosen electron-withdrawing substituents and exhibiting steric hindrance so as to also achieve charge decompression at the surface is therefore demonstrated as a general approach to enhancing the MPC photoabsorption intensity in the optical region. Additionally, we here subject the ligand-enhancement phenomenon to a detailed analysis based on the fragment projection of electronic excited states and on induced transition densities, leading to a better understanding of the physical origin of this phenomenon, thus opening avenues to its more precise control and exploitation.reservedmixedSementa, Luca; Barcaro, Giovanni; Baseggio, Oscar; De Vetta, Martina; Dass, Amala; Aprà, Edoardo; Stener, Mauro; Fortunelli, AlessandroSementa, Luca; Barcaro, Giovanni; Baseggio, Oscar; De Vetta, Martina; Dass, Amala; Aprà, Edoardo; Stener, Mauro; Fortunelli, Alessandr

Ligand-Enhanced Optical Response of Gold Nanomolecules and Its Fragment Projection Analysis: The Case of Au₃₀(SR)₁₈

Here we investigate via first-principles simulations the optical absorption spectra of three different Au₃₀(SR)₁₈ monolayer-protected clusters (MPC): Au₃₀(S^tBu)₁₈, Au₃₀(SPh)₁₈, and Au₃₀(SPh-<i>p</i>NO₂)₁₈. Au₃₀(S^tBu)₁₈ is known in the literature, and its crystal structure is available. In contrast, Au₃₀(SPh)₁₈ and Au₃₀(SPh-<i>p</i>NO₂)₁₈ are two species that have been designed by replacing the <i>tert</i>-butyl organic residues of Au₃₀(S^tBu)₁₈ with aromatic ones so as to investigate the effects of ligand replacement on the optical response of Au nanomolecules. By analogy to a previously studied Au₂₃(SR)₁₆^– anionic species, despite distinct differences in charge and chemical composition, a substantial ligand enhancement of the absorption intensity in the optical region is also obtained for the Au₃₀(SPh-<i>p</i>NO₂)₁₈ MPC. The use of conjugated aromatic ligands with properly chosen electron-withdrawing substituents and exhibiting steric hindrance so as to also achieve charge decompression at the surface is therefore demonstrated as a general approach to enhancing the MPC photoabsorption intensity in the optical region. Additionally, we here subject the ligand-enhancement phenomenon to a detailed analysis based on the fragment projection of electronic excited states and on induced transition densities, leading to a better understanding of the physical origin of this phenomenon, thus opening avenues to its more precise control and exploitation